心筋リガンド感受性K^+チャネルに対するアミオダロンの作用 Effects of amiodarone on ligand-gated K^+ channels in cardiac cells
Amiodarone is one of the most promising antiarrhythmic drugs to reduce likelihood of sudden cardiac death. In this study effects of amiodarone on the ligand-gated K<SUP>+</SUP> channels, i.e., acetylcholine receptor-operated K<SUP>+</SUP> (KACh) channels, ATP-sensitive K<SUP>+</SUP> (KATP) channels and Na<SUP>+</SUP>-activated K<SUP>+</SUP> (KNa) channels, were examined in isolated guinea-pig atrial and ventricular myocytes by patch clamp techniques. Amiodarone in therapeutic concentrations (1-10 μM) inhibited the muscarinic acetylcholine receptor-operated K<SUP>+</SUP> current (IK.ACh) activated by extracellular application of carbachol or adenosine or by intracellular loading of GTPγS to a similar extent in atrial cells.<BR> Amiodarone in similar concentrations inhibited the activity of the KATP channels in inside-out membrane patches of ventricular cells exposed to an ATP-free solution. In a similar concentration range amiodarone also inhibited the opening of the KNa channels in inside-out membrane patches exposed to a high Na<SUP>+</SUP> (100 mM)-containing solution. Thus, these ligand-gated K<SUP>+</SUP> channels are commonly inhibited by amiodarone in the therapeutic concentrations. The inhibitory effects of amiodarone on the ligand-gated K<SUP>+</SUP> channels may play a role in the suppression of cardiac arrhythmias under pathological conditions.
日本薬理学雑誌 106, 77-79, 1995-09-01